1. Field of the Invention
The present invention relates to a pH-sensitive block copolymer that forms polyionic complex (PIC) micelles and a drug or protein carrier using the block copolymer. More specifically, the present invention relates to a pH-sensitive block copolymer that forms nanometer-sized polyionic complex micelles capable of stably containing a drug or protein when administered to a human body through a blood vessel and releasing the drug or protein in response to pH variations at a disease site, and a polymeric micelle-type drug or protein carrier comprising the pH-sensitive block copolymer.
2. Description of the Related Art
Generally, micelles refer to as thermodynamically stable and uniform spherical structures composed of amphiphilic materials (e.g., materials possessing both hydrophilic and hydrophobic groups) of low molecular weight. When a solution of a water insoluble (i.e. hydrophobic) drug is introduced into a compound having a micelle structure, the micelles contain the drug and respond to temperature or pH variations in the body, thus enabling target-specific delivery of the drug. Therefore, the applicability of such micelle type compounds to carriers for drug delivery is considered very high. A key determinant for the applicability of the micelle type compounds is how to stably contain a drug in blood vessels of a human body after administration of a drug through the blood vessel until arrival at a particular disease site, such as a cancer site, to release the drug.
Korean Patent No. 0773078 describes the preparation of micelles using polyethylene glycol and a biodegradable polymer. These constituent materials are advantageously biocompatible due to their biodegradability, but they are not sensitive to changes of particular factors (for example, pH) in the body, making it difficult to deliver a drug to a desired site.
U.S. Pat. No. 6,103,865 discloses a polymer using sulfonamide as a pH-sensitive material. The sulfonamide becomes insoluble at pH≦7.4 but it is ionized and shows acidity at pH>7.4. Since the pH-dependent characteristics of the polymer are opposite to the pH characteristics of cancer cells as targets, the use of a basic compound in the polymer is needed to target the cancer cells. It is known that the pH environment of the body is typically maintained at 7.2-7.4 but the ambient environment of abnormal cells such as cancer cells is weakly acidic (pH 6.0-7.2). In recent years, studies have been done on the specific delivery of drugs to cancer cells at pH<7.2. However, the description that the polymer disclosed in U.S. Pat. No. 6,103,865 can contain a drug and efficiently deliver the drug to a disease site in response to pH variations cannot be found in the specification of the patent because of the poor ability of the polymer to form complexes with the drug.
U.S. Pat. No. 7,427,394 B2 discusses the preparation and application of a biodegradable poly(β-amino ester) compound that is designed to have ester groups associated with biodegradability and tertiary amine groups ionizable at particular pH values in the backbone thereof. The poly(β-amino ester) compound has the advantage that the water solubility varies depending on pH. However, there is no description regarding efficient utilization of the poly(β-amino ester) compound as a drug carrier based on the ionization characteristics.
Under these circumstances, there is a need to develop a copolymer capable of stably containing a drug or protein upon administration to a human body through a route of administration such as a blood vessel and efficiently delivering the drug or protein to a disease site, and a drug or protein carrier using the copolymer.